ArticlePloS one2012
Influence of various polymorphic variants of cytochrome P450 oxidoreductase (POR) on drug metabolic activity of CYP3A4 and CYP2B6.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- The role of cytochrome P450 genetic variants in pesticide metabolism and the risk of child neurodevelopment: a systematic review.Frontiers in pediatrics · 2025Pooled it
- Common Polymorphisms of CYP2B6 Influence Stereoselective Bupropion Disposition.Clinical pharmacology and therapeutics · 2019Trial
- Candidate-gene-based study of CYP3A-related single-nucleotide polymorphisms using 4β-hydroxycholesterol/cholesterol ratio as biomarker in a Japanese cohort.European journal of clinical pharmacology · 2026Article
- The impact of the exposome on cytochrome P450-mediated drug metabolism.Frontiers in pharmacology · 2025Review
- Cyclophosphamide Pharmacogenomic Variation in Cancer Treatment and Its Effect on Bioactivation and Pharmacokinetics.Advances in pharmacological and pharmaceutical sciences · 2024Review
- Article
- Expression ofMedicina (Kaunas, Lithuania) · 2023Article
- Methadone pharmacogenetics in vitro and in vivo: Metabolism by CYP2B6 polymorphic variants and genetic variability in paediatric disposition.British journal of clinical pharmacology · 2022Article
- Relationship between CYP3A5 Polymorphism and Tacrolimus Blood Concentration Changes in Allogeneic Hematopoietic Stem Cell Transplant Recipients during Continuous Infusion.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Stereoselective Bupropion Hydroxylation by Cytochrome P450 CYP2B6 and Cytochrome P450 Oxidoreductase Genetic Variants.Drug metabolism and disposition: the biological fate of chemicals · 2020Article
- Pharmacogenomics of poor drug metabolism in Greyhounds: Cytochrome P450 (CYP) 2B11 genetic variation, breed distribution, and functional characterization.Scientific reports · 2020Article
- NADPH-cytochrome P450 reductase expression and enzymatic activity in primary-like human hepatocytes and HepG2 cells for in vitro biotransformation studies.Clinical hemorheology and microcirculation · 2019Article
- Cytochrome P450 and flavin-containing monooxygenase families: age-dependent differences in expression and functional activity.Pediatric research · 2018Article
- Orchestrated Domain Movement in Catalysis by Cytochrome P450 Reductase.Scientific reports · 2017Article
- Article
- The P450 oxidoreductase (POR) rs2868177 and cytochrome P450 (CYP) 2B6*6 polymorphisms contribute to the interindividual variability in human CYP2B6 activity.European journal of clinical pharmacology · 2016Article
- The POR rs1057868-rs2868177 GC-GT diplotype is associated with high tacrolimus concentrations in early post-renal transplant recipients.Acta pharmacologica Sinica · 2016Article
- Correlation of Cytochrome P450 Oxidoreductase Expression with the Expression of 10 Isoforms of Cytochrome P450 in Human Liver.Drug metabolism and disposition: the biological fate of chemicals · 2016Article
- Interactions between CYP3A5*3 and POR*28 polymorphisms and lipid lowering response with atorvastatin.Clinical drug investigation · 2015Article
- Electron transfer by human wild-type and A287P mutant P450 oxidoreductase assessed by transient kinetics: functional basis of P450 oxidoreductase deficiency.The Biochemical journal · 2015Article
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5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cytochrome P450 oxidoreductase (POR) is known as the sole electron donor in the metabolism of drugs by cytochrome P450 (CYP) enzymes in human. However, little is known about the effect of polymorphic variants of POR on drug metabolic activities of CYP3A4 and CYP2B6. In order to better understand the mechanism of the activity of CYPs affected by polymorphic variants of POR, six full-length mutants of POR (e.g., Y181D, A287P, K49N, A115V, S244C and G413S) were designed and then co-expressed with CYP3A4 and CYP2B6 in the baculovirus-Sf9 insect cells to determine their kinetic parameters. Surprisingly, both mutants, Y181D and A287P in POR completely inhibited the CYP3A4 activity with testosterone, while the catalytic activity of CYP2B6 with bupropion was reduced to approximately ~70% of wild-type activity by Y181D and A287P mutations. In addition, the mutant K49N of POR increased the CLint (Vmax/Km) of CYP3A4 up to more than 31% of wild-type, while it reduced the catalytic efficiency of CYP2B6 to 74% of wild-type. Moreover, CLint values of CYP3A4-POR (A115V, G413S) were increased up to 36% and 65% of wild-type respectively. However, there were no appreciable effects observed by the remaining two mutants of POR (i.e., A115V and G413S) on activities of CYP2B6. In conclusion, the extent to which the catalytic activities of CYP were altered did not only depend on the specific POR mutations but also on the isoforms of different CYP redox partners. Thereby, we proposed that the POR-mutant patients should be carefully monitored for the activity of CYP3A4 and CYP2B6 on the prescribed medication.
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